Improved colorimetric determination of salicylic acid and its metabolites in urine. We describe an improvement in the Levy and Procknal method [J. Pharm. Sci. 57, 1330 (1968)] for determination of salicylic acid and its metabolites in urine. Salicylic acid and salicyluric acid are successively extracted from 1 or 2 ml of urine (acidified with HCl) by two 10-ml portions each of carbon tetrachloride and ethylene dichloride. The extracts of each solvent are shaken with 5 ml of ferric nitrate solution (a 10-fold dilution of 17 g of Fe(NO-3)-9H-2O in 1 liter of 70 mmol/liter HNO-3). The aqueous phases are centrifuged and their absorbances measured at 530 nm. For total salicylate, 3 ml of urine and 3 ml of HCl are heated in a partially evacuated serum vial at 100 degrees C for 16 h and then salicylic acid is assayed in the hydrolyzed sample. Recovery of a weighed oral dose of sodium salicylate in urine was 105.4%; it was 127.9% by the Levy and Procknal method for the same sample. The improved method is faster and more accurate.


Standardization of incubation time and temperature for eight radioimmunoassays. We wanted to know if incubation time and temperature for many radioimmunoassay methods could be standardized, to decrease assay time and so improve efficiency. Percentage binding was determined for triiodothyronine, thyroxine, digoxin, digitoxin, testosterone, aldosterone, estradiol, and diphenylhydantoin when the reaction mixtures were incubated at 6-8, 22, or 37 degrees C for various periods of time. In all methods tested, binding of antigen to antibody was greatest when the reaction mixtures were incubated at 6-8 degrees C, less at 22 degrees C, and least at 36 degrees C. Maximum binding occurred within 30-60 min at each temperature for all methods tested. Hence, it is possible to standardize the incubation time and temperature for these eight radioimmunoassay methods to 60 min at 6-8 degrees C.


Modification of a commercially available digoxin radioimmunoassay kit for higher precision. The procedure prescribed for the Schwarz/Mann 125-l-digoxin kit was modified with regard to pipetting and counting procedure. Incubation time with dextran-coated charcoal was also investigated. The modifications resulted in a significantly higher precision wihout introduction of a systematic error and the analysis time per eight-tube batch was decreased by 20 min.


A versatile temperature-controlled reaction cuvet. A thermostatted reaction cuvet, operating under computerized or manual temperature control in the ultraviolet or visible region, is described and evaluated. The cell was designed for use with the automated chemistry system described earlier [Clin. Chem. 19, 1114 (1973)], but can readily be adapted for other applications. The entire 3-ml cuvet assembly warms from ambient temperature to 37 degrees C in less than 10 min, with plus or minus 0.15 degrees C stability; the long-term stability is plus or minus 0.05 degrees C; temperature recovery time after washing or reagent addition is less than 3 min. The optical pathlength is 10.00 mm and the carryover volume is 18 mu-l.


Alkaloids of tobacco and blood coagulation: effect of nicotine on thrombin and fibrinogen. An alkaloid of tobacco, nicotine, affected the clot-formation property of the enzyme, thrombin, on the substrate, plasma or fibrinogen (thrombin time). Higher concentrations of nicotine retarded the clot-formation property of thrombin. By decreasing the nicotine concentration in the clotting mixture, the clotting time of thrombin was accelerated. Nicotine also modified the clot formation property of plasma or fibrinogen to thrombin, and this effect was dose dependent. From this experimental evidence, it is suggested that nicotine does alter the clot-forming properties of thrombin on fibrinogen.


Sampling problems in the micro determination of blood lead. Sampling tube and fingertip contamination were found to present potential problems in the collection of samples for micro blood lead analyses. Large differences between micro screening and macro confirming lead levels were frequently observed when the time between collection of the two samples was 1-2 weeks. The magnitude of these differences decreased as macro blood lead concentration increased and were apparently a result of episodic lead ingestion in the population.


[Exploratory laparotomy and splenectomy in lymphogranulomatosis (author's transl)]. Exact determination of the extent of the disease is necessary for optimal treatment of lymphogranulomatosis.  To this purpose 53 patients with lymphogranulomatosis had an exploratory laparotomy and splenectomy (42 adults and 11 children).  On the basis of the operation results the pre-operative staging had to be revised in 14 patients and the treatment plan had to be changed in most cases.  Lymphogranulomatosis of the spleen was demonstrable in 27 cases.  Histologically the mixed-cell type was most commonly seen in the spleen.  The size of the spleen was an unreliable diagnostic parameter as regards involvement with lymphogranulomatosis.  In approximately a third of the adults with involved spleens the weight of the spleen was under 200 g.  Hodgkin involvement of the liver was demonstrable in three patients; in these three cases splenic involvement coexisted.  In seven patients post-operative complications occurred.


[Abrasion cytology of the stomach (author's transl)]. Cytological smears from 779 cases were examined over a three-year period, cell collection and cytological diagnosis being in separate hands (material sent in from outside). Three quarters of the cytological findings could be compared with the histological diagnosis: 68% of 194 histologically proven malignant tumours were diagnosed cytologically. The diagnostic accuracy varied between 53 and 74.4%, depending on experience and precision of the endoscopist. In 18 cytologically positive cases results were different from the histological diagnosis. Initial diagnosis of malignant tumour by cytology was made in 3.6% of cases. Subsequently repeated biopsies or histological examination of surgical specimens confirmed the diagnosis.


[Late results of nephropexy for nephroptosis according to a new indication schema]. A new schema for indicating operative treatment of nephroptosis is suggested.  It was validated by an analysis of late results of 37 patients: 32 were completely free of symptoms, three still had the same symptoms but previously present pyelonephritis had healed.  Two patients without long-term antibiotic treatment still had complaints and positive bacteriological findings.  Non of the patients had haematuria.  In two hypertensives the blood pressure had become normal.


[Cerebellar ataxia due to hypothyroidism in adults (case report)]. Cerebellar ataxia was diagnosed in a 62-year-old woman, its signs regressing almost completely within six weeks during treatment with thyroxine and triiodothyronine.  The cause of cerebellar ataxia in association with hypothyroidism remains unknown.  No typical morphological changes in the cerebellum have been described.  It is assumed that a thyrogenic, specific metabolic factor is responsible which aggravates already existing non-specific cerebellar changes.  The prognosis is very good.  On the other hand, cerebellar ataxia resulting from congenital hypothyroidism has typical histological cerebellar changes and prognosis is very poor unless thyroid treatment is started soon after birth.


Gene transfer in Caulobacter crescentus: polarized inheritance of genetic markers. Recombination frequencies were determined for 15 independently isolated auxotrophs of C. crescentus crossed pairwise in all possible combinations. The results indicate that the mutants may be grouped into at least two types: "fertile" strains, which recombine with all other mutants at frequencies ranging from less than 10-6 to 3 times 10-2, and "nonfertile" strains which recombine with fertile strains at high frequencies and with other nonfertile strains at low or negligible frequencies. Several lines of evidence indicate a polarized inheritance of markers. Two of these are (1) the preferential inheritance of unselected markers from the nonfertile parent in fertile times nonfertile crosses, and (2) the consistent ordering of markers based on the frequency at which the mutants recombine with each of the three fertile strains. Although the evidence is not conclusive at this point, the results are most consistent with conjugation at the mechanism of gene transfer in these bacteria.


A mutant affecting meiosis in Neurospora. Many mutants affecting meiosis increase the occurrence of aneuploid meiotic products. In Neurospora, mutants of this type cause ascospore abortion which is reflected by an increase in the proportion of ascospores failing to develop black pigment. The usefulness of the criterion white-ascospore-production as a signal for the presence of a mutant affecting meiosis is demonstrated by the recovery of several such mutants. One of these is mei-1 (meiotic-1), a recessive mutant on linkage group IV. Crosses homozygous for mei-1 produce 90% white ascospores (vs. 5% in wild-type crosses). Viable ascospores, invariably black, are always disomic for one or more linkage groups; the chromatids assorted into viable ascospores do not engage in crossing over in meiosis. The distribution of viable ascospores in individual asci suggests that all meioses are defective in the first meiotic division, and that most meioses are defective in both divisions.


A suppressor gene involved in chemical induction of conjugation in Paramecium aurelia. A dominant gene Su(kau-2) partially suppresses the effect of an apparently unlinked recessive kau-2. Gene kau-2 blocks chemical induction of conjugation in Paramecium aurelia syngen 8 when solutions of acriflavine + either KCl or MgCl-2 are used. Wild-type cells are induced to conjugate in either solution. When cells homozygous for kau-2 also have gene Su(kau-2), they are still uninducible in the solution containing KCl, but become inducible in the MgCl-2 solution. Analysis of the concentrations of solutions which are effective in induction of conjugation of various genotypes shows that the action of Su(kau-2) is not a simple restoration of wild-type phenotype since certain novel features of the suppressor can be seen. Analysis of the duration of ciliary reversal of various genotypes suggests that one necessary step in chemical induction of conjugation is a certain magnitude of depolarization of the surface membrane of the cell.


Correlated responses to selection for postweaning gain in the rat. Evidence for correlated responses to selection was investigated in lines of rats selected for 13 generations for high (U line) and low (D line) 3-9-week gain in comparison with random-bred control lines (R and C lines). The increase in 3-9-week gain in the U lines was shown to be due largely to an increase in 9-week weight, although 3-week weight also increased in these lines. In the D lines, where a marked decrease in 3-9-week gain was observed, this was found to be due to a large decrease in 9-week weight and no detectable change in 3-week weight. The average 2-week litter weight, a measure of the lactational performance of the dam, was significanly greater in the U lines than in the D lines. Selection for 3-9-week gain in these lines of rats led to changes of litter size at birth in the same direction as that of selection. This resulted in a significantly higher litter size in the U lines than in the D lines. The number of rats alive 2 and 9 weeks of age and the percentage of mated females pupping were similar in the U and D lines but lower in these lines than the random bred C lines, providing evidence for a reduction of "fitness" in the selected lines. Carcass composition was studied for all lines at the 11th generation of selection. Carcass composition, in terms of water, fat, ash and protein, was similar in the R and C lines. The U lines had more water and lesss fat than the R or C line. The D lines had similar carcass composition to the R and C lines. It is suggested that these selected and random-bred lines of rats are potentially useful animals to investigate further the developmental and physiological mechanisms which control growth.


Direct response to selection for postweaning gain in the rat. The effectiveness of selection for 3-9 week gain was examined in a population of rats with a history of past selection for high 3-9 week gain. Lines were selected for high (U line) and low (D line) 3-9 week gain with two replicates of each line. Two randomly selected lines were also kept, one originating from the same base population as the two selected lines (R line) and the other originating from a population that had been randomly mated for the previous 27 generations (C line). Two replicates of each of these lines were kept. After seven generations of selection, a randomly selected line (relaxed line) was formed from each of the two upward- and each of the two downward- selected lines. Results have been presented for 13 generations of selection. The environmental trend for 3-9-week gain, as indicated by the randomly selected R and C lines, was consistently negative in all four lines. Realized heritabilities calculated by deviating the response to selection from the trend in the R or C lines resulted in non-significantly higher values in the D lines than the U lines. Six generations of relaxation of selection indicated no effect of natural selection in the U lines or the D lines. The relative magnitude of the drift, error and common environmental variances were estimated by the methods given by HILL (1971). The estimates of these parameters then led to calculation of the degree of bias in the sampling variances of the realized heritability estimates. As was predicted by HILL (1971), estimates of the variance of realized heritabilities obtained by using standard regression techniques were less than those obtained using HILL'S formulae. The results are discussed in relation to other similar studies with rats and mice.


A note on the variance of the number of loci having a given gene frequency. In a recent not in this journal (MARUYAMA 1973), one of us has considered, for a certain genetic model, the variance of the distribution of the number of loci having a given gene frequency. The formula given is incorrect. This brief note considers this problem and notes the correct solution in one particular case.


On Nei and Roychoudhury's sampling variances of heterozygosity and genetic distance. NEI and ROYCHOUNHARY have developed an inequality relationship between the expected values of (j-x - g)-2 and (ĝ - g)-2 where j-x is a biased and g is an unbiased estimate of population homozygosity g. Their inequality is somewhat weak and can be improved, as is demonstrated in this paper.


[On the facial muscles in Perodicticus potto and Nycticebus coucang (author's transl)]. As descriptions of the facial muscles of lorisiform primates are lacking, the species Perodicticus potto and Nycticebus coucang are examined. The results are compared with other prosimians.


The numbers of vertebrae in three African cercopithecine species. The number of precaudal vertebrae in the three African cercopithecine species are analyzed, with two definitions for thoracic and lumbar vertebrae compared. It is found that generic averages obscure some rather substantial differences at the species level for both Cercopithecus and Cercocebus. Further, when zygapophysis structure is used to define vertebral type, rather than presence or absence of rib facets, there is a substantial change in thoracic and lumbar averages that may be important from a functional (locomotion) standpoint.


Interaction in three generation families, parents as mediators: toward a theoretical perspective. This paper focuses on the development of a theoretical perspective within which it is possible to empirically define parental mediation in interactions between grandparents and grandchildren.  Using socialization theory and studies conducted by the writer and a colleague, eight independent dimensions of parental mediation have been identified.  This makes it possible to develop measurement indices for testing the postulate that parents act as mediators between the grandparent and grandchild generations in socializing both into their respective roles and thereby influencing the nature of their relationship.


Patterns of intergenerational exchange: a developmental approach. A review of the current theoretical literature continues to refute the earlier held viewpoint that the American family is an isolated unit with little or no contact with the extended family. Nine theoretical models are presented supporting the existence of rather definitive patterns of intergenerational exchange. Additionally, explanation is given as to how these patterns of exchange operate between generations and why they change over time. Suggestions are presented why the middle family unit of the three generational system eventually emerges today as the center of power or most influential unit.


Attitudes toward age: an exploration in school-age children. Attitudes toward young, middle-age, and old persons were studied in 1000 children (grades 6, 8, 10, 12).  Three newspaper photographs were presented to the children, who estimated the persons' ages and wrote stories about each photograph in his preferred order.  Scores from a semantic differential which provided three factors, Evaluation, Affect, and Activity-Potency, were used in a three-way analyses of variance to analyze further children's attitudes.  The overriding impression from these findings is that these school children do not share the allegedly general, negative attitude toward old age.  The age estimates showed judgmental accuracy and were remarkably uniform in both central tendency and variation.  The overall order of choice was young person, first; old person, second; and middle-age person, last.


Voluntary and involuntary retirement of aged males and their effect of emotional satisfaction, usefulness, self-image, emotional stability, and interpersonal relationships. There is an ever-growing number of male retirees in the American society. The present study was conducted to try to determine the effect of the voluntary and involuntary retirement on emotional satisfaction, usefulness, self-image, emotional stability, and interpersonal relationships in aged males. Significant differences were found among the participants in each of the areas. Voluntary retirement tends to have a more positive influence on the retiree along each dimension.


Attitudinal orientations of wives toward their husbands' retirement. Most research tends to focus on the husband's attitudes toward retirement while overlooking the wife's evaluation of this event. In this study interviews with wives whose husbands were retired or approaching retirement suggested that a variety of orientations toward their husbands' retirement was present. Some women expressed grave reservations; others looked forward to it; still others had no opinion. It is felt that an understanding of the wife's reaction to her husband's retirement can be useful in understanding the adjustments that both husband and wife may have to make in their relationship to each other.


The limitations of crisis theory as an explanatory mechanism in social gerontology. This study examines five specific assumptions of crisis theory as this orientation relates to the prediction of life satisfaction following retirement. Pre-retirement and post-retirement interviews were conducted with a group of 114 men (mean age 68.2 years) residing in an urban area of central Missouri. The data reveal a significant decline in life satisfaction as predicted. Contrary to the theory, however, no significant changes in role behavior in three related areas-family, voluntary associations, and community--were found subsequent to retirement. In addition, the role changes accompanying retirement were not significantly associated with negative changes in satisfaction. Also, increases in role performance were not significantly related to positive changes in satisfaction. Finally, the correlation between work commitment and change in satisfaction proved negative and non significant. On the other hand, the correlation between work commitment and the desire for subsequent employment was negative and significant. In sum, four of the five assumptions of crisis theory do not receive support on the basis of the data.


Generations and aging: a longitudinal study. This study is a longitudinal investigation of the relationship between age and subjective outlook.  Over the years, a number of theoretical positions have been introduced to either account for or to minimize age differences in attitudes, values and beliefs.  The author has organized these theories of aging into three basic sociological fremeworks or models: the "generations" model, the "age status" model and the "illusion of differences" model.  Using a relatively simple methodological desihn, hypotheses derived from these models were tested through secondary analysis of survey data.  Strong support was found for the "generations" hypothesis, weak support for the "age status" hypothesis, and no support at all for the "illusion of differences" hypothesis.


Use of octylbenzenesulfonate in place of dodecyl sulfate in SDS-polyacrylamid gel electrophoresis. Sodium n-octylbenzene-p-sulfonate was successfully used in place of sodium dodecyl sulfate in SDS-polyacrylamide gel electrophoresis. This modification of the usual technique made it possible to scan the polyacrylamide gel for the distribution of the surfactant by measurement of UV absorption. It was found that a band electrophoresed in advance of the complexes formed between protein polypeptides and the surfactant. The band could be observed even in the absence of protein polypeptide, and was ascribed to micelles derived from surfactant added in excess to the sample solution. The complexes were found to be detectable by scanning at 261 nm, usually with better sensitivity than by scanning at 280 nm. Thus, this modification of SDS-polyacrylamide gel electrophoresis is useful both to investigate what is going on in the gel during electrophoresis and to improve the sensitivity of detection by UV scanning of protein complexes.


Neutral glycosphingolipids containing mannose from the bivalve Corbicula sandai. 1. A unique subclass of ceramide oligosaccharides from whole tissue of the fresh-water bivalve Corbicula sandai has been isolated. Through the use of chemical, enzymatic, and physical techniques, two novel glycolipids were characterized as mannosyl-beta (1 leads to 4)-glucosyl ceramide and mannosyl-alpha (1 leads to 4)-mannosyl-beta (1 leads to 4)-glucosyl ceramide. 2. The components of fatty acids and long chain bases in the two glycolipids were analyzed by gas-liquid chromatography and were further identified by mass spectrometry. The data show that, with respect to the major components, both lipids have similar caramide moieties.


Isozymes of alpha-amylase in human urine. Some physicochemical properties of crystalline alpha-amylase [EC 3.2.1.1] isolated from normal human urine were investigated. A crystalline preparation of the enzyme was homogeneous on velocity sedimentation, gel filtration, and sodium dodecyl sulfate disc electrophoresis, and its molecular weight was estimated to be 4.5 X 10-4. However, electrophoretic analyses revealed that the crystalline alpha-amylase consisted of at least five isozymes. The implications of the experimental results are discussed.


Electrophoretic separation of tubulin alpha and beta subunits after S-sulfonation. The modification of tubulin cystine and cystine residues to S-sulfocysteines caused a distinct separation of the alpha and beta subunits in a continuous sodium dodecyl sulfate polyacrylamide gel system. The well-separated subunit bands permitted investigation of the phosphorylation of alpha and beta tubulin subunits. The incubation of tubulin fraction with [gamma-32P]ATP demonstrated that both subunits were phosphorylated in vitro. The incorporation of 32-PO4 into sea urchin eggs, however, failed to cause phosphorylation of tubulin in vivo.


Ascorbate-synthesizing system in rat liver microsomes. II. A peptide-bound flavin as the prosthetic group of L-gulono-gamma-lactone oxidase. L-Gulono-gamma-lactone oxidase [EC 1.1.3.8] was purified 80-fold from rat liver microsomes. In confirmation of our previous finding with a cruder preparation, the purified enzyme was shown to contain an L-gulono-gamma-lactone-reducible pigment as a prosthetic group. This pigment was not liberated from the protein by acid ammonium sulfate, 10% trichloroacetic acid or 2 M area, but was effectively released by proteolytic digestion. The pigment thus released showed a reduced-minus-oxidized difference spectrum characteristic of a flavin compound. The pigment was liberated from a trichloroacetic acid-treated preparation of the enzyme by pronase digestion and purified by Florisil column chromatography and paper chromatography. The absorption spectrum as well as the fluorescence emission and excitation spectra of the purified pigment indicated that it was actually a flavin peptide. It was, however, different not only from FMN but also from flavin peptides isolated from other sources such as succinate dehydrogenase [EC 1.3.99.1] and monoamine oxidase [EC 1.4.3.4] as regards the pH dependence of fluorescence intensity and the Rf value on thin-layer chromatography. A preliminary analysis showed that the purified flavin compound contained several amino acid residues. Alkaline photolysis of the purified flavin peptide suggested that the isoalloxazine ring of the flavin is involved in its binding to the peptide. The hypsochromic shift of the absorption peak in the near-ultraviolet region suggested further that the linkage between the flavin and the peptide may be mediated by the 8-methyl group of the isoalloxazine nucleus. It can be concluded that the prosthetic group of gulonolactone oxidase is a flavin which is covalently bound to the enzyme protein.


Intracellular distribution of various enzymes concerned with DNA synthesis from normal and regenerating rat liver, and Yoshida sarcoma. During the fractionation of various enzymes concerned with DNA synthesis from the postmicrosomal supernatant fraction of various tissues, DNA polymerace [EC 2.7.7.7], thymidine kinase [EC 2.7.1.75], dTMP kinase [EC 2.7.4.9], deoxycytidine kinase [EC 2.7.1.74], and deoxycytidine monophosphokinase (dCMP kinase) [EC 2.7.4.14] were found in the pellet fraction of postmicrosomal supernatant. Further, the uridine kinase [EC 2.7.1.48] and aspartate transcarbamylase [EC 2.1.3.2] activities of postmicrosomal supernatant from various tissues were also present in this pellet fraction. The activities of DNA polymerase, thymidine kinase, uridine kinase, and aspartate transcarbamylase from normal and regenerating rat liver, and Yoshida sarcoma were higher in the pellet fraction than in the supernatant. On the other hand, the activities of dTMP kinase, dCMP kinase, and orotidine-5'-phosphate decarboxylase [EC 4.1.1.23] were lower in the pellet fraction than in the supernatant. The pellet fractions of regenerating rat liver and Yoshida sarcoma showed a remarkable incorporation of various precursors (thymidine, dTMP, deoxycytidine, and dCMP) into DNA in the presence of a suitable DNA template, ATP and all four deoxynucleoside 5'-triphosphates for DNA synthesis. Normal adult rat liver catalyzed a much smaller incorporation of all these precursors, except for dCMP.


Purification and properties of acylamino acid-releasing enzyme from rat liver. An enzyme that releases acylamino acid from amino terminal acylated peptides and proteins has been isolated from rat liver in a highly purified form bya six-step procedure comprising extraction from liver homogenate, ammonium-sulfate fractionation, heat treatment, chromatography on columns of DEAE-cellulose and hydroxylapatite and gel filtration on a Sepharose 6B column. About 1,500-fold purification was achieved from the liver homogenate. The purified enzyme preparation showed a single band on polyacrylamide gel disc electrophoresis. The enzyme specifically released acylamino acids from several amino terminal acylated peptides and proteins with different rates of hydrolysis depending on the acyl groups, terminal amino acid sequences and tertiary structure of the acyl protein substrates. The present enzyme may be useful for the removal of the N-terminal acylamino acid from some N-terminal blocked peptides and proteins in amino acid sequence analysis. The molecular weight of the purified enzyme was estimated to be 360,000-420,000 by gel filtration and sucrose density gradient ultracentifugation. Disc electrophoresis of the acylamino acid-releasing enzyme on SDS-polyacrylamide gel suggested that the enzyme consisted of five or six identical subunits having a subunit weight of about 75,000. The N-terminal residue of the subunit, which consisted of a single polypeptide chain, was glycine. Other properties of the enzyme, including isoelectric point, the effects of metal ions and several chemical reagents on the enzyme activity, pH optimum, and amino acid composition were also examined.


Thermodynamic study of a liquid crystal as a liquid phase in gas-liquid chromatography. II. A cholesteric liquid crystal. Gas-liquid chromatography is utilized for the determination of thermodynamic solution parameters for various organic solutes at infinite dilution in the meso- and isotropic phases of cholesteryl palmitate. The thermodynamic data and trends in values of the activity coefficients for the solutes are discussed in relation to their structure and to the orientations of the liquid crystal.


Determination of sulphonamides by electron-capture gas chromatography. Preparation and properties of perfluoroacyl and pentafluorobenzyl derivatives. The derivatization of benzenesulphonamide, N-ethylbenzenesulphonamide and N-phenylbenzenesulphonamide with trifluoroacetic and heptafluorobutyric anhydride and pentafluorobenzyl bromide has been studied. A rapid quantitative acylation is obtained in benzene in the presence of trimethylamine. Pentafluorobenzylation is performed by the extractive alkylation technique using tetrabutylammonium as counter ion and methylene chloride as solvent. Less than 20 min are required for a quantitative derivatization. The derivatized sulphonamides have a hydrophobic character, making them very suitable for gas chromatography. Trifluoroacetylation and heptafluorobenzylation decreases it. The derivatives have a high electron-capture detector response (minimum detectable quantity, 1-2 X 10-minus 16 moles/sec). A standard curve is given for the determination of N-phenylbenzenesulphonamide as trifluoroacetyl derivative in the range 1.8-90 ng/ml.


Simultaneous detection of a wide variety of commonly abused drugs in a urine screening program using thin-layer identification techniques. A single-step extraction method and thin-layer identification techniques capable of testing a wide variety of drugs of abuse are presented. These techniques are well suited for large and/or small drug programs involved in urine testing because they provide substantial economic benefits and improve clinical functioning. The drugs are absorbed on a 6 X 6 cm piece of paper loaded with cation-exchange resin and then eluted from the paper at pH 10.1 using ammonium chloride-ammonia buffer. The simultaneous thin-layer detection of sedatives, hypnotics, narcotic analgesics, central nervous system stimulants and miscellaneous drugs is accomplished by spotting the solution of extracted residue on a 20 X 20 cm Gelman pre-coated silica gel glass microfiber sheet (ITLC Type SA). A two-stage solvent system is used in order to obtain a chromatogram with optimum separation of a wide range of drugs. This system can separate methadone and/or cocaine from propoxyphene, methaqualone, methylphenidate, pentazocine, pipradrol, Doxepin, chlorpromazine, phenazocine, naloxone, naltrexone, imipramine and trimeprazine; amphetamine from phenylpropanolamine and dimethyltryptamine; codeine from dextromethorphan; methamphetamine from dimethyltryptamine, etc. Different detection reagents are then applied in succession to different marked areas of the developed chromatogram. This elegant method of extraction and spraying has enabled us to detect morphine base at a sensitivity level of 0.15 mug/ml, amphetamine sulfate at 1.0 mug/ml, methamphetamine hydrochloride at 0.5 mug/ml, phenmetrazine hydrochloride at 0.5 mug/ml, codeine phosphate at 0.5 mug/ml, methadone hydrochloride at 1.0 mug/ml, secobarbital at 0.36 mug/ml and phenobarbital at 0.5 mug/ml in urine. The minimum volume of urine needed to achieve these sensitivities is 20 ml. The cost of analysis per urine specimen using these techniques for concomitant screening of these drugs is less than US$ 1.


Liquid ion exchangers in paper chromatography of steoidal glucosiduronic acids. Influence of different exchangers on the mobility in chloroform-formamide and correlation of chromatographic data. A group of 25 steroidal glucosiduronic acids was chromatographed on paper chloroform-formamide in the presence of several different liquid ion exchangers. Chromatograms were run also in three Bush-type systems. RF values were converted into RM values and the data were correlated by use of a series of regression equations of the type RM(Y) = a-RM(X) + b, in which X designates a standard system to which each other system (Y) is compared. The ratio of the slope a to the correlation coefficient r (i.e., a/r) is a measure of the resolving power of system Y relative to the standard system; intercept b, in association with slope a, is an indication of the polarity of system Y relative to X. The correlation coefficient r and the standard error of estimate sy-x are indications of whether solvent systems Y and X have very similar or relatively different resolving properties for a group of solutes. The regression equations are useful for correlating chromatographic data obtained from a group of compounds in several solvent systems. Properties of the chromatography systems are discussed and the relative importance of ion exchange and hydrogen bonding with the various solvent systems is pointed out. Delta RMg and delta RMr values are given for functional groups at several locations in the conjugates for ten of the chromatography systems.


Comparison of costs for testing a wide variety of drugs of abuse per urine specimen in a drug abuse urine screening program and frequent urine collections. Existing urine testing techniques in a drug abuse urine screening program with their capacity to analyze urine specimens per day are discussed. The start-up cost using each technique and cost per specimen are presented. A single step extraction technique using ion-exchange paper to absorb drugs prior to thin-layer chromatography (TLC) as reported by these laboratories will cost $0.58 per specimen, for testing the entire aray of drugs of abuse (at least 9-14 tests per specimen). Sensitivity reported using TLC technique for the morphine base is 0.15 mug/ml (minimum volume of urine needed 20 ml), 0.10 mug/ml if the volume of urine available is 30-35 ml, and 0.07 mug/ml if the volume of urine available is 43-50 ml.


Gas chromatographic studies of phenobarbital and diphenylhydantoin after flash-heater alkylation. The functionally excellent flash-heater methylation, ethylation and butylation techniques have been extended to include the higher alkyl homologs. Phenobarbital and diphenylhydantoin have been alkylated using the tetraalkylammonium hydroxides in which the alkyl group ranges from methyl to hexyl. The gas chromatographic properties of the resulting alkyl derivatives have been investigated.


Estimation and identification in blood plasma of paracetamol (N-acetyl-p-aminophenol) in the presence of barbiturates. Barbiturates are a source of interference in the estimation of paracetamol by both UV spectrophotometry and gas-liquid chromatography (GLC). Experiments have shown that the interference by barbiturates on GLC can be avoided by benzoylation (in aqueous solution) of the paracetamol. This O-benzoyl derivative can be N-silylated to give an additional identification parameter. The method, which requires ml of sample, will quantitatively and qualitatively estimate "free" paracetamol in plasma and in post mortem blood in the range of 2-40 mug of drug per millilitre of sample.


Ligand-exchange chromatography of amino acids on copper-, cobalt- and zinc-chelex 100. Procedures for the ligand-exchange chromatography of amino acids on copper-, cobalt-and zinc-Chelex 100 have been examined. Ligand exchange on the copper complex affords a simple and rapid method for the removal of amino acids (except for aspartic and glutamic acids) from dilute solutions. The influence of the pH on the binding of amino acids to the metal complex was also studied. The bound amino acids could be eluted with ammonium hydroxide which also causes a slight metal leakage. Chromatography on cobalt- and zinc-Chelex 100 showed that only the basic amino acids were quantitatively attached to these complexes at pH 8.3-9.5, whereas the others were predominantly EXCLUDED. This procedure can be used for the selective concentration and removal of basic amino acids in the presence of other amino acids.


Comparative gas chromatographic analysis of narcotics. III. Phenmetrazine hydrochloride. Chemical signatures of phenmetrazine hydrochloride were studied by gas chromatography. The inter-batch variations of the signatures were found to be large whereas the intra-batch variations were usually small. The method is used for the tracing of seized phenmetrazine hydrochloride samples to common sources, which in turn may permit further tracing back to chains of illicit distribution of this drug. The applicability of the method to other narcotics is also discussed.


Use of trimethylsilyl and other homologous trialkylsilyl derivatives for the separation and characterization of mono- and dihydroxycannabinoids by combined gas chromatography and mass spectrometry. A gas chromatographic separation of dihydroxy- from monohydroxycannabinoids by the use of homologous trialkylsilyl derivatives is discussed. Trimethylsilyl derivatives produced a group of peaks containing both sets of compounds, sometimes poorly resolved, whereas by increasing the alkyl chain length to n-butyl complete fractionation into two groups, was achieved. The mass spectra of these derivatives resembled those of the trimethylsilyl derivatives with the addition of a set of ions resulting from estimation of the Si-alkyl chains as olefins.


Fatty acids. II. The synthesis and gas-liquid chromatographic behaviour of five trimethylene-interrupted C18-diunsaturated fatty acids. Five trimethylene-interrupted methyl octadecadiynoates, C18 delta-2a,-7a; delta-3a,-8a; delta-4a,-9a; delta-5a,-10a and delta-6a,-11a, and the corresponding cis,cis-octadecadienoates were synthesized, and their gas-liquid chromatographic properties were studied on Apiezon L, diethylene glycol succinate polyester and Silac 10C stationary phases. The equivalent chain lengths of these esters have been determined, and the separation of mixtures and the prediction of gas chromatographic behaviour of these isomers are discussed.


Use of SE-30 as a stationary phase for the gas-liquid chromatography of drugs. The dimethyl silicone elastomer SE-30 has been chosen as the preferred liquid phase for the gas-liquid chromatographic analysis of drugs, and retention index data have been compiled for 480 drugs and commonly occurring chemicals such as plasticisers. The inter-laboratory variation in measurement of retention indices has been measured for three drugs in eleven laboratories and the standard deviations were between 20 and 15 retention index units.


Hereditary angioedema: the use of fresh frozen plasma for prophylaxis in patients undergoing oral surgery. Six patients with hereditary anagioedema (HAE) undergoing 7 episodes of dental surgery received transfusions with fresh frozen plasma one day before surgery. Although the morbidity observed in these patients following similar procedures had been high, no significant complications of surgery were noted with this therapy. Thus, fresh frozen plasma infusion appears to provide a safe and effective method of prophylaxis in patients with HAE. Following infusion of fresh frozen plasma, serum levels of C4 esterase inhibitor (C1EI) rose transiently, and then fell to preinfusion levels within 1 to 12 days. In all but one patient the rise in C4 was greater than could be accounted for by the amount of C4 infused. In no patient did the level of C1EI or C4 rise to within the normal range. The data raise the question of the role of C1EI in the pathogenesis of angioedema in these patients.


Tropical eosinophilia. A human model of parasitic immunopathology, with observations on serum IgE levels before and after treatment. The diverse clinical syndromes characterized by asthmatic symptoms, transient pulmonary infiltrates, and eosinophilia have tended to obscure the specific association of one such entity with filarial infections. Serum IgE levels were determined before and after therapy in a group of well-characterized patients with tropical eosinophilia (TE), studied earlier in Singapore. The mean serum IgE level in 14 cases before treatment with diethylcarbamazine was 2,355 ng. per milliliter, with a trend but statistically nonsignificant decrease in levels to 600-1,000 ng. occurring 8 to 12 weeks after therapy. Leukocyte and eosinophil counts showed a rapid reduction after treatment, and although mean complement-fixing (cf) titers to Dirofilarial antigen tended to decrease, they were not significantly reduced until 5 to 6 weeks. The historical development of evidence supporting the filarial etiology of TE was reviewed. Many basic questions engendered by the clinical syndrome of tropical eosinophilia make it an excellent model for study of the immunopathology of parasitic infections.


The chronicity of acute attacks of asthma--mechanical and therapeutic implications. Defects in ventilatory function can persist for considerable periods of time following the amelicoration of the signs and symptoms of acute episodes of asthma. Serial spirographic and lung volume determinations in such patients demonstrate that the pattern of resolution of these abnormalities is such that their subtlest manifestations are depressed flow rates in the mid vital capacity range and/or elevations in residual volumes. These changes are believed to represent the effects of residual obstruction that is located in the airways in the periphery of the lung. Recent studies suggest that this residua is capable of influencing the lung's response to asthmogenic stimulis, and imply that it may be beneficial to place asthmatics on continuous therapy for as long as they have alterations in lung function.


Release of osteoclast activating factor by normal human peripheral blood leukocytes. A reliable method for obtaining osteoclast activating factor (OAF) in the culture medium of phytohemagglutinin-activated peripheral blood leukocytes is described. OAF was detected by its ability to stimulate resorption of fetal rat bone in organ culture. Most bone resorbing activity was released by activated leukocytes during the first 24 hours of culture, well before -3H-thymidine incorporation was increased. Cultures maintained for longer than 3 days showed a decrease in OAF activity. Stimulated leukocytes cultured in medium with as little as 0.01 per cent plasma showed increased -3H-thymidine incorporation and released as much OAF as leukocytes cultured with 20 per cent plasma. OAF release was stimulated by pokeweed mitogen and concanavalin A as well as by phytohemagglutinin.


Persistent effects of chenodeoxycholic acid on biliary lipids in the hamster. The effects of feeding chenodeoxycholic acid (CDC) on biliary lipid composition, on the rate-limiting enzymes of hepatic cholesterol and bile acid synthesis, and on hepatic cholesterol and bile acids were determined in hamsters. The goals were to study the mechanism and duration of the cholesterol desaturation action of CDC. Administration of CDC for 30 days significantly increased the biliary bile acid and lecithin to cholesterol ratio and the percentage of CDC in bile (p less than 0.01). These effects persisted for 20 days after discontinuing CDC (p less than 0.01) and were no longer evident at 30 days. HMG CoA reductase and 7 alpha-hydroxylase activities were significantly reduced by CDC (p less than 0.01). After discontinuing CDC, these effects persisted for 10 days at which time HMG CoA reductase was still decreased by 50 per cent (p less than 0.01) and 7 alpha-hydroxylase by only 12 per cent (p less than 0.01) and were no longer evident by 20 days. Hepatic cholesterol did not change, while hepatic CDC was significantly elevated throughout the experiment. (1) CDC has a salutory effect on biliary lipid composition while causing an increase of exogenous CDC in bile and a decrease of endogenous cholesterol synthesis. (2) The persistence of decreased cholesterol synthesis and of improved biliary lipid composistion after discontinuing CDC provides a rationale for studying this in man and then testing intermittent CDC regimes for gallstone dissolution.


Calcium absorption as a function of calcium intake. The relationships between the amount of calcium absorbed and the quantity ingested was evaluated in 180 adult humans. Absorption was measured from the concentration ratio of concurrently administered oral and intravenous calcium isotopes. Intake ranged from 0.163 to 7.48 Gm. Ca per day. In 14 subjects, intakes were artificially elevated for purposes of this study. All others were studied at their usual intake levels. Absorption (Ca Abs) was found to follow a curvillnear relationship with intake (Ca-D), and was characterized by the following equation: Ca Abs equals 0.1541 - Ca-D plus 0.3127[exp(-1.0539 - Ca-D)] - Ca-D. The exponential term of this equation provided the major component of total absorption at intakes below 0.8 Gm. per day, but fell to negligible values when intake reached 2 to 3 Gm. per day, above which absorption was characterized by a simple linear function of intake. We found that there was no detectable upper limit to absorption capacity, which, at the 7.48 Gm. intake level, averaged more than 1.0 Gm per day. The observed mathematical description is consistent with the generally recognized inverse relationship between absorption efficiency and intake. At the same time it indicates that a component of absorption is independent of control mechanisms and is related solely to intake. A more general form of the foregoing equation, suggesting provision for other physiological variables such as growth hormone and cortisol, is proposed and discussed.


Globin synthesis in subjects doubly heterozygous for hemoglobin G-Philadelphia and hemoglobin S or C. To study the function of globin-chain genes, in vitro synthesis of globin was measured in reticulocytes concentrated from the peripheral blood of 7 subjects doubly heterozygous for an alpha-chain abnormality (Hb G-Philadelphia) and a beta-chain abnormality (Hb S or C). Each had a deficit of alpha-chain synthesis compatible with an alpha-thalassemia-like syndrome. The data are also compatible with the quantitative expression of variable reduplication of the alpha-chain locus in man.


Efferent pathways of the coronary chemoreflex. This study was performed to identify the efferent pathways which mediate vasodilation during activation of the coronary chemoreflex and to compare the reflex responses in vessels in skeletal muscle and skin. Reflex vasodilator responses (decreases in perfusion pressure) were measured in innervated, perfused gracilis muscle and hindpaw of dogs during activation of the coronary chemoreflex with intracoronary injections of nicotine. Reflex vasodilator responses to intracoronary nicotine (1.25 and 2.50 mu-g per kilogram) averaged -14 plus or minus 5 (S.E.M.) and -34 plus or minus 6 mm. Hg, respectively, in muscle, but only -5 plus or minus 2 and -10 plus or minus 4 mm. Hg, respectively, in paw. Atropine, tripelennamine, and propranolol did not alter the vasodilation. Guanethidine blocked reflex vasodilation in muscle. The reflex vasodilator responses in paw were slight and were not significantly attenuated by guanethidine. The results indicate that sympathetic cholinergic pathways to skeletal muscle do not participate in the coronary chemoreflex. The reflex vasodilation in muscle results from withdrawal of adrenergic constrictor tone. The efferent pathway demonstrates that the coronary chemoreflex does not produce striking withdrawal of adrenergic tone in paw. The results indicate, therefore, that activation of the coronary chemoreflex results in greater withdrawal of adrenergic constrictor tone and greater vasodilation in muscle than in skin.


Comparative value of L-, and D-methionine supplementation of an oat-based diet for humans. Total sulfur-containing amino acids have been found to be the first limiting amino acid in several foods in comparison with human amino acid requirements. Addition of methionine in appropriate amounts to these foods might be expected to improve protein value. Economically, DL-methionine would be preferable to L-methionine for this purpose. However, the comparative tuilization of L- DL-, and D-methionine is unclear. The objective of the current project was to compare the effectiveness of L-, DL-, and D-methionine supplementation of diets based on a food product known to be low in methionine value for human subjects. "Instant" oatmeal was fed to adult subjects to provide 4.0 g of nitrogen/day. In randomly arranged periods, these diets were supplemented with L-, DL-, or D-methionine at two levels (0.58 and 1.16 g of methionine/day). An unsupplemented diet was used in a control period. Diets were adequate in vitamins, minerals, and energy. Mean nitrogen balances of subjects while receiving the L-methionine supplements at the 0.58 and 1.16 g levels were minus0.10 and +0.06 g of nitrogen, respectively. At similar levels of DL-methionine supplementation, nitrogen balances were minus0.12 and minus0.15 g of nitrogen, respectively, and minus0.24 and minus0.18 g of nitrogen with D-methionine supplementation. The mean nitrogen balance when no supplement was used was minus0.22 g of nitrogen. Thus, D-methionine is seemingly poorly utilized by the human. Urinary methionine excretion data supported these results.


Effect of supplements of zinc salts on the healing of granulating wounds in the rat and guinea pig. It has now been universally accepted that zinc deficiency interferes in some way with wound healing, but the claims that the addition of zinc supplements to the normally nourished rat accelerates wound healing to super-normal levels has, on investigations, produced contradictory results. In this study the rate of healing of granulating wounds on the backs of two species of animals, the rat and the guinea pig, has been studied when supplements of zinc salts were given in association with a normal diet. The zinc supplements were administered either orally, parenterally, or topically. There was no difference in the rate of healing in either species of animal given zinc supplements by any of the routes used.


Effect of micelle formation on the absorption of neutral fat and fatty acids by the chicken. Experiments were conducted to determine the absorption of various dietary fatty acids and glycerides singly and in mixtures. Chickens with or without cannulated bile ducts or ligated pancreatic ducts were used to evaluate the absorption of fatty acids or mixtures of fatty acids and the absorption patterns of several classes of lipids and their effect on the absorption of palmitic acid under in vivo conditions. In spite of wide melting point differences, isomers of various monoglycerides or 18-carbon unsaturated fatty acids exhibited identical absorption and solubility patterns. A homologous series of saturated monoglycerides showed a maximum absorption value for the monoglycerides with fatty acids of 12 and 14 carbons. Absorption decreased with increasing chain lengths of the fatty acid in the monoglyceride. Conversely, the absorption of palmitic acid when fed with the various monoglycerides progressively increased to a maximum in the mixture containing monomyristin and then decreased when fed with monopalmitin or monostearin.


Developmental changes in the distribution of rat liver ribosomes in response to dietary manipulations. Ribosomal profiles were prepared from liver postmitochondrial supernatant preparations of 2- to 21-day old and 60-day-old rats. Rats fed or starved for 3 or 15 to 16 hours were compared. Relative ribosomal distribution, calculated from planimetric analysis of the hepatic ribosomal profiles, was found to be approximately constant at all ages when fed animals were compared. In contrast, starvation for 15 hours resulted in profound changes in ribosomal distribution, i.e., a relative accumulation of oligosomes as compared with polysomes. This change in ribosomal distribution was most extensive in animals younger than 2 weeks of age, 60-day-old rats showing no effect. Refeeding of 6-day-old starved rats with diets containing 10% protein resulted in a prompt decrease in the planimetric yield of monsomes and disomes. Similarly, dietary protein was shown to be required to prevent accumulation of these two species. It is suggested that it is the response of the ribosomal cycle to starvation that changes with age rather than the maximum capacity for protein synthesis.


Effects of various dietary levels of dried whey on the performance of growing pigs. Because dried whey contains approximately 70% lactose, it could be harmful if incorporated into the diet of animals with low tolerance for lactose. Three experiments were conducted to determine the effects of various levels of dried whey in the diet of growing pigs. In the first two experiments diets containing up to 40% dried whey were fed from weaning to approximately 5 months of age. With respect to rate of gain or feed efficiency, there were no significant differences among dietary treatment groups. In a third experiment pigs that had consumed a diet containing no lactose from 6 to 12 weeks of age performed normally when fed a diet containing 40% dried whey from 12 to 21 weeks of age. The results of the three experiments suggest that the growing pig can tolerate up to 30% lactose in the diet without any symptoms of lactose intolerance, and that continuous exposure to lactose in the diet is not necessary to maintain tolerance to this level of lactose.


Histological alterations in tryptophan-deficient rainbow trout. Tryptophan-deficient and nondeficient synthetic amino acid test diets were prepared using D, L-amino acids. The diets were fed to three groups of rainbow trout (Salmo gairdneri) for 8 weeks. Experimental control fish fed well and grew from 1.3 to 2.5 g. Deficient fish fed poorly and did not gain weight. Scoliosis was observed in the deficient fish after 1 week of feeding. Daily transitory scoliosis was noted in some fish. Histological studies of trypthophan-deficient scoliotic fish revealed hyperemia, disorganization of myomere septa, and protrusions of the fibrous matrix sheath, which invests the notochord. Abnormal deposition of calcium was noted in the kidney and the bony plates surrounding the notochord and sheath. Fish with mechanically induced scoliosis had disorganization of myomere septa, but did not have protrusions of fibrous matrix sheath, nor did they have abnormal calcium deposition in bone or kidney. Scoliotic fish returned to normal within 1 week upon replacement of tryptophan in the ration.


Intestinal absorption of free and protein-bound dietary methionine in the rat. Intestinal absorption of radioactive free and protein-bound dietary methionine (Met) and changes in plasma amino acids were observed after feeding Met-supplemented test meals. Plasma and gastrointestinal contents were collected from 15 minutes to 16 hours after feeding. Plasma amino acids were determined after ad libitum ingestion of diets containing free Met. Protein-bound Met in fresh egg white and free Met left the stomach at the same rate, but protein-bound Met in dried egg white and free Met were emptied from the stomach at different rates. Free Met was absorbed from the intestine more rapidly than protein-bound Met. Concentrations and molar ratios of various free amino acids in plasma changed briefly in response to Met-supplemented single test meals. Long-term changes were observed when Met-supplemented diets were fed ad libitum. Prolonged ingestion of supplemented diets may cause sustained alterations in the plasma amino acid pattern.


Effects of high risk and low risk diets for colon carcinogenesis on fecal microflora and steroids in man. We investigated the effects of a high meat mixed Western diet and a nonmeat diet, representing the dietary pattern of high and low risk areas for colon cancer, respectively, on fecal microflora dn on bile acid and neutral sterol patterns in man. The total anaerobic microflora as well as the count of Bacteroides, Bifidobacterium, Peptococcus, and anaerobic Lactobacillus were significantly higher during the period of consumption of a high meat mixed Western diet comparted with the nonmeat-diet consumption period. The difference in total fecal bile acid excretion was not significant between the two dietary periods. Fecal excretion of microbially modified bile acids and neutral sterols was decreased when subjects eating a high meat diet transferred to a nonmeat diet. These results support the fact that diet plays a modifying role on the composition of intestinal microflora, bile acids, and neutral sterols.


Protein synthesis in liver, muscle, and brain of rats fed a high tyrosine-low protein diet. Effects of feeding rats a high tyrosine-low protein diet on protein synthesis in liver, muscle, and brain were investigated both in vitro and in vivo. Tissue tyrosine concentrations of rats consuming the high tyrosine diet for 7 days were substantially elevated; this was accompanied by severe growth retardation. In the livers of rats fed the high tyrosine diet for 6 days, polysomal profiles showed a shift toward heavier ribosomal aggregates, while in muscle and brain, extensive disaggregation of polysomes occurred. In an in vitro amino acid incorporating system, the activities of both the microsomal and pH 5 enzyme fractions isolated from the livers of the high tyrosine animals that had been fed the diet for 6 weeks were elevated. On the other hand, the capacity of muscle or brain ribosomal preparations to incorporate [14-C] leucine was much reduced. Similar results were obtained in a study of [14-C] leucine incorporation in vivo in which rats were force-fed two meals and killed at various times after the last feeding. In rats fed the high tyrosine diet, incorporation of leucine into liver increased progressively; this was accompanied by a gradual decrease in leucine incorporation into muscle. In contrast, leucine incorporation into brain was immediately suppressed. In view of the apparently paradoxical effect of a high tyrosine load on protein synthesis in the liver, rates of the anabolic and catabolic phases of protein turnover in animals fed a high tyrosine diet were determined from radioactivity measurements made after pulse labeling them with [14-C] bicarbonate. Results indicated that the rates of both synthesis and degradation of liver proteins were elevated over control values. Differences in the effects of a toxic load of tyrosine on protein synthesis in the tissues examined could be the consequence of altered metabolic or hormonal balance as a result of nutritional stress.


Effects of sucrose feeding on the intestinal transport of sugars in two strains of rats. The rates of intestinal transport of dietary monosaccharides and disaccharides were determined in Wistar rats and the carbohydrate-sensitive BHE rats fed either a stock diet or a 65% sucrose diet. Sucrose-fed rats of both strains generally showed large and significant increases in the rates of glucose, alpha-methylglucose, fructose, and sucrose transport. The transport of galactose, maltose, and lactose did not show consistent increases due to sucrose feeding. Although the magnitude of the increases in sugar transport due to sucrose feeding was only slightly greater in BHE rats than in Wistar rats, BHE rats tended to exhibit a greater rate of sugar trnasport when fed both strains and in the BHE rats fed the stock diet. Lipogenic enzyme activity was greatly increased as a result of sucrose feeding; however, BHE rats did not show greater levels of enzyme activity than did Wistar rats. Liver lipids were increased in both the Wistar and the BHE sucrose-fed rats and in BHE rats fed either diet.


Nitrogen balance of men with marginal intakes of protein and energy. Present protein allowances are based on amounts of nitrogen (N) that maintain balance in adults in laboratory tests. In most tests of minimum N need, energy intakes were higher than present allowances and generally the participants maintained body weight or gained. To evaluate the relative importance of energy and protein intakes in the near-adequate range on the N equilibrium, healthy men were given two levels of protein with energy constant and three levels of energy with protein constant. In the first two 12-day periods, diets provided 5 and 7% of energy (E) from egg white protein with enough E to maintain weight essentially constant (39.6 plus or minus 4.4 kcal/kg). N balance data with these diets were used to select an individual protein intake level nearest to need (5, 6, or 7%), and that level was fed for the next three periods with the same E intake as before (100 E) and 85 or 115% of it. Crude N balance (dietary-fecal-urinary N) was minus0.26 g/day with 5% diet and 0.33 g/day with 7%. Balance was improved by 280 mg/g N fed between these levels. Predicted minimum N need to maintain crude N balance at 100 E is 89 plus or minus 18 mg/kg body weight or 3.76 plus or minus 0.61 mg/basal kcal. N balance fell to minus0.61 g/day with 85 E and increased to 0.59 g/day with 115 E. N balance changed by 174 mg/100 kcal between 85 and 100 E and 112 mg/100 kcal between 100 and 115 E. Energy intake appears to have a much greater effect on N balance than does protein intake in the marginally adequate ranges of intake.


Effect of dietary cholesterol on hepatic lipogenesis and plasma insulin and free fatty acid levels in rats. In order to further investigate the metabolic alterations in the liver of cholesterol-fed rats, the following parameters were determined: (a) the activities of hepatic glucose-6-phosphate dehydrogenase, NADP-malate dehydrogenase, citrate cleavage enzyme, acetyl CoC carboxylase, and fatty acid synthetase; (b) the rate of hepatic fatty acids synthesis in vivo or in vitro; and (c) the concentration of immunoreactive insulin, free fatty acids, and glucose in the plasma. The experimental diets usually contained 1.5% cholesterol and 0.5% cholic acid. Cholesterol feeding resulted in a three- to fourfold decrease in the activities of hepatic glucose-6-phosphate dehydrogenase, NADP-malate dehydrogenase, and citrate cleavage enzyme and up to a two-fold decrease in the activities of acetyl CoA carboxylase and fatty acid synthetase. The rate of fatty acid synthesis was not sifnigicantly decreased when rats were fed the cholesterol-supplemented diets for only 2 to 4 weeks, despite marked decreases in the activities of the lipogenic enzymes. But when cholesterol feeding was continued for periods longer than 5 weeks, there was a significant decrease in the rate of fatty acid synthesis in the liver. Cholesterol feeding decreased the levels of circulating insulin and elevated plasma free fatty acid levels. Plasma glucose levels were not significantly changed. Cholesterol feeding can result in a wide range of metabolic alterations. These metabolic alterations may have some impact on the development of hypercholesterolemic-related metabolic disorders.


Sugar transport and metabolism in Schistosoma mansoni. The absorption kinetics of some 14-C-labeled simple sugards in adults of Schistosoma mansoni are described. The influx of fructose and 3-0-methylglucose was by diffusion alone, while glucose, 2-deoxyglucose (2DOG), galactose, glucosamine, and mannose were absorbed by mediated transport as well as by diffusion. Although absorbed glucose was rapidly metabolized, uptake rates of radio-glucose in 2-min incubations corresponded with the amount of glucose (determined chemically) removed from the incubation medium. In 30-min incubations 2DOG was slowly metabolized and accumulated against an apparent concentration difference. The mediated transport of glucose and 2DOG was inhibited in Na+-free media, and by the presence of ouabain, phlorizin, phloretin, and other sugars. Accordingly, influxes of glucose of 2DOG and 22-Na+ were coupled. On a per mg protein basis, female worms transported more 2DOG and glucose, but less glycine, than did males. However, the rate of glucose metabolism by male and female worms incubated together was greater than that of either males or females incubated separately. The nature of sugar transport in schistosomes and other flatworms is similar to that in vertebrates.


Developmental physiology of cestodes. XIV. Roughage and carbohydrate content of host diet for optimal growth and development of Hymenolepis diminuta. Diets of rats infected with Hymenolepis diminuta (CESTODA: Cyclophyllidea) were altered with respect to carbohydrate content and to roughage, and the effects on worm growth and development were studied. Compared to worms from rats fed a 56% glucose diet, those on a 56% starch diet were heavier at 10 and 15 days and had more immature proglottids at 5 days, mature prglottids at 10 days, and mature and gravid proglottids at 15 days postinfection. In addition, worms from rats fed the starch diet contained a higher carbohydrate concentration and a lower lipid concentration from those fed the glucose diet. Worms from rats fed diets with combinations of carbohydrates such as 51% starch-5% sucrose and 51% starch-5% lactose were not different from those fed the 56% starch diet. If rats were fed a pellet diet (Purina Laboratory Chow), the worms grew substantially larger than those from rats fed the 56% starch or combination diets. The differences could be overcome if a 6% roughage component were included in the 56% starch diet. Therefore, the starch-roughage diet here presented is recommended as the optimal defined diet for studies of the development of H. diminuta in the definitive host.


Henneguya sebasta sp. n. (protozoa, myxosporida) from California rockfish, Sebastes spp. Henneguya sebasta sp. n. was found on the bulbus and truncus arteriosus and in the heart chambers of 7 species of marine rockfish, Sebastes, from central and southern California. The incidence of this parasite may be of economic interest to the sport and commercial fisheries because of its possible pathogenicity.


Survival of Ancylostoma caninum on bluegrass pasture. The survival of infective larvae of Ancylostoma caninum on outdoor grass plots was studied in 40 experiments over 1 year. Weather data were collected over the period. Mean larval survival from August to early November was 24 days (range 1 to 49), from December through February was 0 days, and from March to mid-August was 6.6 days (range 0 to 21). Moderate to high temperatures and substantial rainfall favored larval survival; low temperatures and rainfall favored larval destruction.


The ultrastructure of adult Brugia malayi (Brug, 1927) (Nematoda: Filarioidea). The ultrastruct of the adult subperiodic Brugia malayi (Brug, 1927) within pulmonary arteries of male jirds (Meriones unguiculatus) was studied by transmission electron microscopy. The cuticle consists of 10 sublayers (2 of which are prominently banded) and a typical outer unit membrane. Evidence is presented showing that the subcuticular region of the lateral chords comprises a functional complex of basal infoldings, multivesicular bodies, and associated mitochondria, which is probably engaged in the exchange of solutes across a permeable cuticle. Microbodies with paired, prominent cores, intracisternal A-particle viruslike bodies, nonstaining glycogen patches, and other structures are also present in the lateral chords. The platymyarian somatic musculature shares some coelomyarian characteristics, e.g., apparent neuromuscular connections and prominent glycogen deposits surrounded by mitochondria and other organelles. The alimentary tract has features typical of many nematodes. The luminal segments of the male and female reproductive tracts and their germinal products, excluding microfilariae, are described. Affinities with related species are discussed.


Differential responses of Duroc, Hampshire, and crossbred pigs to a superimposed experimental infection with the intestinal threadworm, Strongyloides ransomi. In both spring and fall, 12 Duroc, 12 Hampshire, and 12 Duroc times Hampshire F1 weanling pigs all reared under the same management were fed in pens of 3 to slaughter weights. Three Duroc and 4 Hampshire boars, essentially unrelated within breed, were used in sampling the breeds. Swine herd management allowed pig infection with Strongyloides ransomi and Ascaris suum, but neither clinical nor subclinical parasitism was evident in the herd. Pigs were percutaneously exposed by pens within breed and season, half to none (control) and half to 3,000,000 (exposed) S. ransomi infective larvae, Breed, treatment, and seasons were prominent sources of variation in pig response. Breeds failed to respond alike to parasitism in respect to experimental periods and exposure levels. This interaction response (P smaller than 0.01) showed that S. ransomi egg production increased rapidly for all breed groups but decreased quicker and greater in Durocs, slowest and least in Hampshires, with cross breds intermediate in these respects. The 2.0830 for mean of log A. suum EPG from exposed Durocs was near double that of control Durocs but the mean for exposed Hampshires was less than half that for controls; crossbreds tended to be intermediate in this respect. Daily gains of 0.70 and 0.73 for Durocs and crossbreds were similar (P greater than 0.10) but averaged 11.7% more (P smaller than 0.05) than the 0.64 kg for Hampshires and gains by control pigs were 20.6% above (P greater than 0.01) that of exposed pigs. Exposed pigs required more feed per kg of gain (P greater than 0.05) than control pigs (3.60 vs. 3.33 kg). Comparison of relative gains and feed efficiences of control and exposed pigs among and within breed groups supported the position that a superimposed exposure of 3,000,000 S. ransomi larvae was more severe for Hampshires, intermediate for crossbreds, and least severe for Durocs.


Spontaneous and synaptic excitation of paramedian reticular neurones in the decerebrate cat. 1. In decerebrate cats neurones in the region of the paramedian reticular nucleus were identified by responses to stimulation of implanted cerebellar electrodes. Approximately one half were antidromically activated and one half orthodromically. 2. Somatic stimulation and electrical stimulation of both hind limb and cranial nerves activated many of these cells. There was no correlation between the effects of these stimuli on cell firing and on blood pressure. 3. A number of rhythms in spontaneous firing were observed. One fifth of cells fired with the rhythm of efferent activity in the recurrent laryngeal nerve. In animals showing cycles of stability and instability in blood pressure corresponding phases of activity and inactivity in the firing of paramedian reticular neurones were observed. 4. Most paramedian reticular cells showed bursts of firing preceding abrupt rises in blood pressure but this was also observed with cells lateral to this area. 5. One third of cells studied showed changes in firing rate correlated with the changes in blood pressure which followed I.V. acetylcholine and noradrenaline. 6. Bilateral carotid artery occlusion, which always produced a rise in blood pressure, had little effect on cell firing.


The spinal course and distribution of fore and hind limb muscle afferent projections to the superior colliculus of the cat. 1. Projections to the superior colliculus from fore and hind limb muscle nerves have been examined. 2. Hind leg nerve stimulation at strengths sufficient to excite Group II and III fibres elicited unit discharge in all layers of the superior colliculus and underlying tegmentum. 3. Forelimb nerve stimulation excited units in all layers of the superior colliculus and underlying tegmentum. Twenty per cent were activated by stimulation below Group II threshold, the remainder by stimulation above Group II threshold. 4. Most units activated by limb afferent nerve stimulation were also activated by visual stimuli. There was considerable convergence from both flexor and extensor nerves and most units were excited by stimulation of nerves in more than one limb. 5. Units fired either with a short or long latency or with a paired discharge. Short latency units were most common in deep collicular layers and the tegmentum, long latency units were most common in superficial layers. 6. The spinal pathway of the afferents is mainly in the dorsolateral quadrant contralateral to the recording site. The anatomical characteristics of the pathway are similar to the lateral funiculus climbing fibrespinocerebellar pathway.


The sensitivity of paramedian reticular neurones to acetylcholine. 1. Of paramedian reticular neurones a significantly higher proportion of those antidromically activated from the cerebellum than of those orthodromically activated from this source were excited by acetylcholine. 2. Receptors for acetylcholine were of the muscarinic type. 3. No differences were found in the proportions of cholinoceptive and non-cholinoceptive cells responding to stimulation of cranial and limb nerves or to changes in blood pressure either spontaneous or induced. 4. Either a cholinergic pathway to paramedian reticular cells projecting to the cerebellum was not activated in these experiments or the receptors for acetylcholine are not located at synapses. An association between muscarinic receptors and acetylcholinesterase may be present with cells of this area.


The inulin space, solute concentrations, and weight changes in rat renal medullary slices incubated in iso-osmolal media, and their modification during anoxia and hypothermia. 1. The volume of distribution of [14-C]carboxyl inulin has been studied in slices of outer and inner medulla from rat kidney incubated in Krebs phosphate-bicarbonate Ringer, modified to render it iso-osmolal with the tissue fluids in these zones, under three conditions, (a) aerobically at 37 degrees C (control), (b) anoxically at 37 degrees C, and (c) aerobically at 0 degrees C. 2. Under control conditions near steady-state volumes of approximately 24 and 42 mul./100 mg wet weight slice were obtained for outer and inner medulla respectively during the period 10-30 min from the start of incubation. In the outer medulla the volumes of distribution in anoxic and hypothermic slices exceeded that in control slices during this time, but control values increased from 30 to 100 min so that after 100 min the distribution volumes were approximately 30 mul./100 mg under each set of conditions. 3. In the inner medulla control and anoxic slices had inulin distribution volumes of approximately 42 mul./100 mg during 10-30 min, rising to over 50 mul./u99 mg by 100 min. Slices incubated hypothermically reached a steady-state value of approximately 40 mul./100 mg by 30 min, which did not increase further for up to 100 min. 4. All slices lost about 10% of their initial weight during the first 3 min of incubation. Thereafter control slices maintained weight constancy for at least 30 min (outer medulla) or 100 min (inner medulla); slices incubated anoxically or hypothermically gained weight, the gains being greatest in anoxic outer and hypothermic inner medulla. 5. The K concentration within control slices (both zones), hypothermic outer and anoxic inner medulla attained equilibrium when slice [K] was approximately 8 times medium [K] (5-9 mM). In anoxic outer and hypothermic inner medullary slices [K] fell to a significantly greater extent, but interpretation of these findings in terms of slice K loss is subject to modification in respect of the increases in slice weight (water content) accompanying the [K] decreases. 6. There was a transient (1-3 min) rise in [Na] in all slices. This was followed by a [Na] decrease, which was most apparent in control slices, and finally a gradual increase towards medium [Na] (141 and 180 mM for outer and inner medulla respectively).


Volume adjustment by renal medullary cells in hypo- and hyperosmolal solutions containing permeant and impermeant solutes. 1. The changes in the volumes of cells in slices (thickness 0-3-0-4 mm) of rat renal outer and inner medulla have been investigated during aerobic incubation for 20 min at 37 degrees C in Krebs phosphate-bicarbonate Ringer modified by the addition of urea or sucrose in order to produce a range of media hypo- and hyperosmolal with respect to the calculated tissue fluid osmolalities in these regions. 2. On the assumption that under these conditions the measured inulin space approximates to the true extracellular space (ECS), it was found that osmotic swelling or shrinkage of cells was not accompanied by any significant variation in the absolute size of the ECS. 3. Calculated cell volume changes in both regions were minimal when slices were incubated in urea-containing media iso-osmolal with tissue fluids in that region. In sucrose-containing media minimal cell volume changes occurred when media were hypo-osmolal in relation to tissue fluids by a factor of approximately 0-68. 4. In all except the most hypo-osmolal media studied, calculated cell volume changes (as percentage of initial volume) were linearly related to the reciprocal of the incubation media osmolalities. The points of interception of the regression lines on the cell volume axis were dependent upon both the region studied and the composition of the incubation medium (urea or sucrose). 5. These changes were accompanied by variations in slice solute concentrations. Slice [Na] was greatest, and slice [K] least, following incubation in those media producing the greatest percentage changes in cell volume. 6. The volume of distribution [14-C]sucrose within the inner medulla was 61-7 plus or minus 2-5 mul./100 mg wet weight of tissue (mean plus or minus S.E., n equals 6) after 10 min incubation. The increase to 70-8 plus or minus 4-2 mul./100 mg (n equals 6) after 100 min was not significant (0-1 greater than P greater than 0-05). The volume of distribution within the outer medulla rose markedly during this period, from 38-1 to 58-2 mul./100 mg.


Setting priorities in developing an affirmative action program. "Affirmative action" programs call for special activities to ensure that women and minorities participate in employment and educational opportunities in the numbers in which qualified members of these groups are represented in the nation or community. Six kinds of activities should receive priority in establishing a medical school affirmative action program: (a) review of salaries for equity, (b) establishing goals for hiring in both faculty and nonfaculty jobs, (c) review of admissions criteria to assure that women and minorities are not required to meet a higher standard than white males to include accurate predictors of the success of applicants from these groups, (d) survey of physical facilities to assure that lounges and facilities for women are equivalent to quality and convenience to those available to men, (e) examination of employment and instructional policies to identify any which have a "disparate effect" on the success of women and minorities and modification of such policies wherever alternatives are possible, (f) review of staff, student, and administrative attitudes to assure that the institutional atmosphere conveys support of equal opportunity. Success in accomplishing each of these priorities will build a basis for success in other aspects of the equal opportunity program.


Implementing university hospital ambulatory care evaluation. The clinics of a single university hospital center were observed to determine a practical rationale for and impediments to implementing a medical care evaluation program. A quality assurance mechanism is especially important in the ambulatory care setting because of problems with patient compliance, lack of policy continuity, lack of intercommunication among care providers, no counterpart for most inpatient quality-oriented activities, structural defects in many clinics, and general emphasis on the inpatient medicine. Impediments to implementing quality assurance programs include the condition of clinic records and individual charts, lack of established criteria for care, problems of care provider intercommunication during the evaluation process, manpower availability, choice of evaluation method, and method of implementing resulting plans for corrective action.


Socialization of health proffessionals in Israel: early sources of congruence and differentiation. In the longitudinal study reported here a comparison was made of changes in basic professional orientations of students during the first three years of professional socialization four health fields in Israel: medicine, dentistry, pharmacy, and nursing. Data are analyzed from the same groups at three points: prior to entry, at the end of year one, and at the end of year three. The image of the "competent" professional is analyzed in terms of a set of underlying traits which in all four populations are shown to group themselves empirically into three dominant components: People, Science, and Status. The priorities accorded to these components are quite similar in all four professions, suggesting a common basic orientation among them. The analysis also points to different levels of absolute emphasis on the components and to changes in patterns of emphasis during the early stages of socilization.


The use of pass/fail grades to assess academic achievement and house staff performance. The advantages of a formal grading system in assessing a student's capability to practice medicine remain controversial. Students prefer the pass/fail method, while faculty lean toward the traditional approach. The efficacy of a modified pass/fail grading system in detecting superior academic achievement, as well as in predicting house staff performance, was evaluated. Mean scores on the examinations of the National Board of Medical Examiners of students selected fo Alpha Omega Alpha were significantly higher than those of other students, although the faculty was unaware of these results when selecting candidates. Chairmen in institutions where 125 students had served their first graduate year of training felt that 85 percent of the dean's letters summarizing the student's academic performance over a three-year period accurately indicated subsequent performance on the house staff. These results suggest that a modified pass/fail grading system can detect superior students as well as provide relevant information with respect to subsequent performance as a physician.


Dimensions of medical students' perceptions of instruction. Factor analysis of medical student ratings of basic science instruction yielded three dimensions of student perception of instruction: faculty-student rapport, outside work, and aspects of student comprehension. While these factors are similar to those identified in other studies, they differ in respects probably reflecting differences between medical students and other students and differences in questionnaire design.


A pair comparison study of the relevance of nine basic science courses. A judgment of the relevance of nine basic sciences courses was tested by the pair comparison method. The test groups consisted of first-, second-, third-, and fourth-year medical students; interns and residents; basic sciences faculty; and clinical faculty. The data obtained from all groups proved to be consistent. Three strata of relevance were detected. Physiology, pathology, and pharmacology comprised the stratum of maximum relevance. The anatomy sciences (gross anatomy, histology, cell biology, and embryology) formed a stratum of lowest relevancy. The comparative relevancy of biochemisty and microbiology fell between the two extremes. Two approaches for making the anatomy disciplines more relevant are discussed.


Recruitment and progress of minority medical school entrants 1970-1972. This is a report on a national study of minority group applicants and entrants to the 1970, 1971, and 1972 entering classes of U.S. medical colleges. The aim of the investigation was to further understanding of the factors involved in attempting to increase minority representation in education for the practice of medicine. Data from the Association of American Medical Colleges are used to examine characteristics of successful and unsuccessful minority applicants to medical school. Socieconomic, personal, institutiona, and geographical factors that relate to the recruitment and progress of minority students in medicine are analyzed and evaluated. Differences between Caucasian and minority group students affecting admissions, retention, and promotion are documented. The investigators also compare the projections of a 1970 AAMC task force report with actual occurrences in the national effort to expand educational opportunities in medicine for blacks and other underrepresented minority students (that is, American Indians, Mexican Americans, and mainland Puerto Ricans). This comparison shows substantial progress toward the projected figures but a need for renewed commitment if they are to be reached. Suggestions are offered for improving the recruitment and progress of minority medical school entrants by such means as the AAMC Simulated Minority Admissions Exercises and by ongoing programs at individual medical schools. The study also yielded such pertinent findings as the following: 1. Confirmation that the racial characterizations self-reported by medical school applicants have a high degree of accuracy and an increasing degree of completeness. 2. An encouraging increase in the number of black premedical students who will potentially apply for the medical school classes entering in 1976 and 1977. 3. Growth in the enrollment of low-income medical students, most of it explained by the increase in the numbers of minority group members who have been admitted in recent years. 4. More mobility among blacks than Caucasians with regard to attending medical schools in other than their region of legal residence. 5. A higher proportion of women, of older, and of married students among minority medical school matriculants than among Caucasian matriculants. 6. A slightly higher medical school retention rate for Caucasians than for students from underrepresented minority groups, possibly explained in part by the greater diversity in the socioeconomic and educational backgrounds of the latter. 7. A positive relationship for blacks between the size of undergraduate college attended and successful completion of the first year of medical school.


Clinical styles and motivation: a study of laboratory test use. The study reported in this paper examines clinical reasoning styles with a focus on laboratory utilization. A stratified sample of 80 physicians participated in the solution of a simulated patient management problem. The analysis focuses on variation in the portfolio of laboratory tests ordered as a function of practice setting (e,g., physicians in practice versus physicians in training). The study also examines the response of physicians to the imposition of constraints on ordering, as well as behavior, when unlimited ordering capacity is provided. Overall, the data profiles emerging from the analysis indicate the variety inherent in physician decision-making strategies, and point to the necessity of employing a cautious and flexible approach toward any general scheme of constraints upon medical diagnostic procedures;


Cholecystectomy peer review: measurement of four variables. Process and outcome analyses were carried out on a group of patients who had uncomplicated cholecystectomy. The postoperative length of stay and patient satisfaction were also measured. A random sample of 80 charts was selected from 222 eligible records for process analysis. Outcome was evaluated in 218 of the 222 eligible patients against explicit criteria. More patients were in the symptomatic and back-to-work group than expected. The peer consensus was that these results were not related to the surgical procedure or specifically related to gallbladder disease. Ninety-five per cent of the patients assessed care as good or excellent, and 90 per cent felt the length of postoperative stay was satisfactory. When the patients were divided according to surgeon, significant differences in the length of postoperative stay were found in the 154 patients without common bile duct exploration. After the findings were presented to the surgeons through an educational program, changes occurred which resulted in a decrease of nearly one day in the postoperative hospitalization.


Measuring of the quality of health care: a decision oriented typology. Numerous methodologies have been devised to measure various aspects of the quality of health care. Revised bibliographies of articles of articles reporting these methodologies are made available periodically. This paper is an attempt to devise a use ful framework for cataloguing these methods in order that health care planners and administrators can readily assess the means available to quantify aspects of health care under their scrutiny. A decision tree is presented for the decision maker to follow through according to his requirements, and a discussion presents a brief summary of the methods in each particular category. Gaps indicating the need for further research are identified.


The use of item importance weights in assessing physician performance with predetermined criteria indices. Conditions for using single measures or combinations of measures of physician performance are discussed. Studies reporting combination indices of proficiency are reviewed for their use of equally or differentially weighted components and for the use of these with many or with single diagnoses, Comparisons of diagnostic-specific measures are made using differential and equal item weights. Under the general conditions of this research, few psychometric differences existed. The use and acceptability of differential item weights in this research are also discussed.


Absence of an effect of chronic administration of growth hormone on serum lipids. Human growth hormone (hGH) was administered to a group of osteoporotic patients at two dosage levels for a period of 6 mo each. The first dose employed was 2 units subcutaneously daily, and the second dose was 0.2W-3/4 units (where W is body weight expressed in kg) daily. There was no significant change in serum-cholesterol or triglyceride concentration despite the production of hyperglycemia and soft-tissue swelling on the higher dosage regimen. A number of factors may account for the conflict between our findings and a previous report in which hGH administration had a lypocholesterolemic, hyperglyceridemic effect. These factors include differences in sex, age, dosage, and duration of treatment. Nonetheless, it is clear that from a therapeutic vantage, even if hGH were readily available, it would not be a useful hypocholesterolemic agent.


Turnover of plasma-free arachidonic and oleic acids in resting and exercising human subjects. Turnover rates and metabolism in the leg region and the splanchnic region, of free arachidonic and oleic acid have been examined in five healthy subjects at rest and during bicycle exercise. A continuous intravenous infusion of tritiated arachidonic acid and 14-C-labeled oleic acid was given. The rate constant for arachidonic acid turnover at rest was 0.44 plus or minus 0.004/min as compared to 0.29 plus or minus 0.02 for oleic acid. Significant correlations between turnover rate and arterial concentrations were observed for both acids in the resting state. The turnover of arachidonic acid was not significantly altered during exercise which caused an eight- to ninefold rise in pulmonary oxygen uptake. In contrast, the turnover of oleic acid rose markedly with exercise; its rate constant increased by approximately 90% to 0.57 plus or minus 0.05/min. The fractional uptakes of the two acids in the leg region were similar in the resting state. The splanchnic fractional uptake for arachidonic acid significantly exceeded that for oleic acid at rest. There was a net uptake of arachidonic acid in the splanchnic region in all subjects studied. In vitro incubations of whole blood deomonstrated a significant exchange of arachidonic as well as oleic acid between plasma and blood cells. We conclude that the metabolism of plasma free arachidonic acid differs from that of oleic acid in that (1) its fractional turnover at rest is about 50% higher, (2) its splanchnic fractional uptake is about 60% higher, and (3) its turnover rate is unaffected by physical exercise. It is further suggested that the high turnover rate of arachidonic acid, and to a less extent that of oleic acid, could be due in part to an exchange of fatty acids between plasma and endothelial cells.


Dose-response study of the inhibiting effect of somatostatin on growth hormone and insulin secretion in normal subjects and acromegalic patients. A dose-response study of the effect of somatostatin on plasma growth hormone (GH) and immunoreactive insulin (IRI) levels was performed in normal subjects and acromegalic patients. In normal subjects 150 mug of somatostatin completly suppressed GH and IRI responses to arginine, while with 75 and 37.5 mug only a partial suppression was usually observed. Basal levels of plasma IRI were significantly lowered within 15 min from the start of somatostatin injection at each of the three dose levels. In three acromegalics the doses of 150 and 75 mug of somatostatin were effective in lowering both GH and IRI levels; the dose of 37.5 mug was still effective in lowering plasma IRI levels, while GH levels were not significantly modified. A dose of somatostatin inhibiting GH secretion without affecting insulin secretion has not been found either in acromegalics and in normals. It was concluded that the effects of somatostatin on GH and IRI secretion cannot be easily dissociated.


Serum lipids in acromegaly.

Serum lipids in acromegaly. Serum cholesterol and triglyceride concentrations were determined in 46 patients with active acromegaly but with otherwise intact pituitary function. The mean serum-cholesterol level of the patients was lower and the mean serum-triglyceride higher than in the basic population of comparable age. The incidence of hypercholesterolemia was similar to that in general population, whereas the incidence of type IV hypertriglyceridemia was almost three times higher than in control population. The serum triglyceride level was not related to relative body weight, basal serum growth hormone, or insulin concentrations, nor did it correlate with glucose tolerance or with plasma-insulin response to oral glucose. However, the patients with highest plasma-insulin response had significantly higher serum triglyceride than the rest of the acromegalic group. The endogenous serum-triglyceride turnover rate showed no consistent changes, but increased serum triglyceride was associated with increased production rate. Upon successful surgical treatment of the acromegaly, serum-triglyceride level decreased in most of the cases who initially had hypertriglyceridemia. It is concluded that acromeagaly can give rise to moderate secondary hypertriglyceridemia.


Comparative response to parathyroid hormone in hyperthyroidism and hypothyroidism. The effects of exogenous parathyroid hormone, administered for 3 days, were compared in six hyperthyroid and six hypothyroid subjects. Maximum increments were much greater in hyperthyroid than in hypothyroid subjects for serum calcium (3.5 mg/100 ml versus 1.6 mg/100 ml), urine calcium (476 mg versus 79 mg), urine hydroxyproline (56 mg versus 11 mg), and urine phosphorus (671 mg versus 192 mg). Maximum decrease in serum phosphorus (minus0.9 mg/100 ml versus minus 0.1 mg/100 ml) was also greater in hyperthyroid subjects. Serum parathyroid hormone immunoreactivity was significantly higher in hypothyroid subjects (0.48 ng/ml) that either normals (0.21 ng/ml) or hyperthyroid subjects (0.19 ng/ml). The data support the concept that excess thyroid hormone sensitizes and deficient thyroid hormone blunts the responsiveness of bone to parathyroid hormone. This may lead to a state of hypoparathyroidism in hyperthyroidism and hyperparathyroidism in hypothyroidism.


Effects of calcium infusions in patients with postmenopausal osteoporosis. From earlier studies, it appeared that postmenopausal women with osteoporosis may not be so responsive to therapeutic calcium infusions as younger men. A study of seven women with postmenopausal osteoporosis revealed that only one had a good therapeutic response as judged by sustained decrease in bone pain and improvement in calcium balance. It is concluded that a series of calcium infusions is unlikely to be therapeutically useful in postmenopausal osteoporosis.